Since cardiopulmonary and hepatic vascular lesions produced by monocrotaline appear to be self perpetuating following the inital injury, it is important to elucidate the means by which this is accomplished. In our work to date it appears that dehydroretronecine, the major detectable metabolite of monocrotaline, does not produce vascular lesions in the heart, lung and liver of rats following injection of a single large dose or repeated small doses in the tail vein or portal vein. Since this metabolite reacts with macromolecules in vivo and in vitro under acidic conditions, it seems likely that the pH of the liver, lung and heart are not ideal for any appreciable binding. To data it has not been possible to label monocrotaline, and monocrotaline pyrrole is too labile a compound with which to work. The semisynthetic pyrrolizidine alkaloid, disenecioyl retronecine has been prepared in our laboratory (Hsu and Allem, J. Labelled Compounds, in press). This compound has been shown to cause vascular lesions similar to those produced by monocrotaline. In addition, the labeling of this compound on the l-hydroxy methyl group makes it possible to follow its interaction with cellular components. During the coming year we plan to determine the specific cells of the lungs, heart and liver that are affected by the above pyrrolizidine alkaloid. Secondly, we will determine the interaction of metabolites with cellular macromolecules in order to clarify their specific mode of action.